(R)-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)propanoic acid | 167308-62-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)propanoic acid
• 英文别名: 3-[[(4R)-2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl]amino]propanoic acid
• CAS: 167308-62-5
• 化学式: C₁₂H₂₁NO₅
• 分子量: 259.302
• InChiKey: DIJFLMYTVZNQAU-VIFPVBQESA-N

物化性质

• 熔点：
  88-90 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  453.7±45.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)propanoic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 35.0h， 生成 S-acetoacetyl-pantetheine
  参考文献：
  名称：

  酰基辅酶A底物的化学酶法合成使小分子和蛋白质的原位标记成为可能。

  摘要：

  描述了一种化学酶促方法，其产生全功能的酰基辅酶A分子，然后将其用作底物以驱动原位酰基转移反应。还说明了基于质谱的测定法，以验证酰基辅酶A酶产物的身份。该方法响应于可以修饰为其相应的辅酶A硫酯的各种羧酸，在利用酰基辅酶A底物的广泛化学生物学研究中具有潜在的应用前景。

  DOI：

  10.1021/acs.orglett.5b02113
• 作为产物：
  描述：

  D-(-)-泛酰内酯 在 正丁基锂 、 palladium 10% on activated carbon 、 氨 、 氢气 、 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 苯 为溶剂， 反应 43.08h， 生成 (R)-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)propanoic acid
  参考文献：
  名称：

  Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801

  摘要：

  The fast and efficient syntheses of pantothenic acid and the antiparasitic agent CJ-15,801 have been achieved starting from a common imide unit through the selective manipulation of enamide intermediates.

  DOI：

  10.1021/ol103114w

文献信息

• Acyl-group specificity of AHL synthases involved in quorum-sensing in <i>Roseobacter</i> group bacteria
  作者：Lisa Ziesche、Jan Rinkel、Jeroen S Dickschat、Stefan Schulz

  DOI：10.3762/bjoc.14.112

  日期：——

  N-Acylhomoserine lactones (AHLs) are important bacterial messengers, mediating different bacterial traits by quorum sensing in a cell-density dependent manner. AHLs are also produced by many bacteria of the marine Roseobacter group, which constitutes a large group within the marine microbiome. Often, specific mixtures of AHLs differing in chain length and oxidation status are produced by bacteria, but how the biosynthetic enzymes, LuxI homologs, are selecting the correct acyl precursors is largely unknown. We have analyzed the AHL production in Dinoroseobacter shibae and three Phaeobacter inhibens strains, revealing strain-specific mixtures. Although large differences were present between the species, the fatty acid profiles, the pool for the acyl precursors for AHL biosynthesis, were very similar. To test the acyl-chain selectivity, the three enzymes LuxI₁ and LuxI₂ from D. shibae DFL-12 as well as PgaI₂ from P. inhibens DSM 17395 were heterologously expressed in E. coli and the enzymes isolated for in vitro incubation experiments. The enzymes readily accepted shortened acyl coenzyme A analogs, N-pantothenoylcysteamine thioesters of fatty acids (PCEs). Fifteen PCEs were synthesized, varying in chain length from C₄ to C₂₀, the degree of unsaturation and also including unusual acid esters, e.g., 2E,11Z-C18:2-PCE. The latter served as a precursor of the major AHL of D. shibae DFL-12 LuxI₁, 2E,11Z-C18:2-homoserine lactone (HSL). Incubation experiments revealed that PgaI₂ accepts all substrates except C₄ and C₂₀-PCE. Competition experiments demonstrated a preference of this enzyme for C₁₀ and C₁₂ PCEs. In contrast, the LuxI enzymes of D. shibae are more selective. While 2E,11Z-C18:2-PCE is preferentially accepted by LuxI₁, all other PCEs were not, except for the shorter, saturated C₁₀–C₁₄-PCEs. The AHL synthase LuxI₂ accepted only C₁₄ PCE and 3-hydroxydecanoyl-PCE. In summary, chain-length selectivity in AHLs can vary between different AHL enzymes. Both, a broad substrate acceptance and tuned specificity occur in the investigated enzymes.

  N-酰基脱氨核糖乳酸（AHLs）是重要的细菌信使，在细胞密度依赖的方式中介导不同的细菌特征。AHLs也被许多海洋玫瑰细菌组的细菌产生，这在海洋微生物组中占据着一个大的群体。通常，细菌会产生具有不同链长和氧化状态的AHLs的特定混合物，但是生物合成酶LuxI同源物如何选择正确的酰前体大部分是未知的。我们分析了Dinoroseobacter shibae和三株Phaeobacter inhibens菌株中的AHL产生，揭示了菌株特异性混合物。尽管这些物种之间存在很大差异，但脂肪酸谱，即AHL生物合成的酰前体池，非常相似。为了测试酰链选择性，从D. shibae DFL-12的三种酶LuxI1和LuxI2以及从P. inhibens DSM 17395的PgaI2在大肠杆菌中异源表达，并将酶分离用于体外孵育实验。这些酶容易接受缩短的酰辅酶A类似物，即脂肪酸的泛酸半胱氨基乙酰硫酯（PCEs）。合成了15种PCEs，链长从C4到C20不等，不饱和度不同，还包括不寻常的酸酯，例如2E,11Z-C18:2-PCE。后者作为D. shibae DFL-12 LuxI1的主要AHL的前体，2E,11Z-C18:2-脱氨核糖乳酸（HSL）。孵育实验表明，PgaI2接受除C4和C20-PCE之外的所有底物。竞争实验表明，这种酶对C10和C12 PCE有偏好。相比之下，D. shibae的LuxI酶更具选择性。虽然2E,11Z-C18:2-PCE优先被LuxI1接受，但除了较短的饱和C10-C14-PCE之外，所有其他PCE都不被接受。AHL合酶LuxI2仅接受C14 PCE和3-羟基癸酰-PCE。总之，AHL中的链长选择性在不同的AHL酶之间可能有所不同。在研究的酶中既有广泛的底物接受性，也有调节的特异性。
• Step-Economic Synthesis of Biomimetic β-Ketopolyene Thioesters and Demonstration of Their Usefulness in Enzymatic Biosynthesis Studies
  作者：Johannes Wunderlich、Theresa Roß、Marius Schröder、Frank Hahn

  DOI：10.1021/acs.orglett.0c01348

  日期：2020.7.2

  by limited access to appropriate substrate surrogates. We present a step-economic synthetic access to biomimetic β-ketopolyene thioesters that is based on an Ir-catalyzed reductive Horner–Wadsworth–Emmons olefination. New β-ketotriene and pentaenethioates of pantetheine and N-acetylcysteamine were exemplarily synthesized via short and concise routes. The usefulness of these compounds was demonstrated

  多烯硫酯中间体的生物合成工艺研究由于难以获得合适的底物替代物而变得复杂。我们提出了一种仿生的β-酮多烯硫酯的逐步经济合成方法，该方法基于Ir催化的还原性Horner-Wadsworth-Emmons烯烃化反应。示例性地通过简短的途径合成泛酸的新的β-酮三烯和戊烯硫醚以及N-乙酰基半胱胺。这些化合物的有用性在体外测定中得到了证明，该酮还原酶结构域来自Mycolactone生物合成的MycKRB。
• Sulfonate/Nitro Bearing Methylmalonyl-Thioester Isosteres Applied to Methylmalonyl-CoA Decarboxylase Structure–Function Studies
  作者：Lee M. Stunkard、Austin D. Dixon、Tyler J. Huth、Jeremy R. Lohman

  DOI：10.1021/jacs.9b00650

  日期：2019.4.3

  ester or amide. Structures of Escherichia coli methylmalonyl-CoA decarboxylase in complex with our analogs affords insight into substrate binding and the catalytic mechanism. Counterintuitively, the negatively charged sulfonate and nitronate functional groups of our analogs bind in an active site hydrophobic pocket. Upon decarboxylation the enolate intermediate is protonated by a histidine preventing CO2-enolate

  丙二酰-硫酯是丙二酰-CoA 和丙二酰-S-酰基载体蛋白的反应中心，对脂肪酸、聚酮化合物和各种专门的代谢物生物合成必不可少。产生或使用丙二酰硫酯的酶会在晶体学时间范围内自发地水解或脱羧反应物，从而阻止确定结构-功能关系。为了解决这个问题，我们合成了一组甲基丙二酰辅酶A类似物，其中羧酸盐由磺酸盐或硝基表示，硫酯保留或由酯或酰胺表示。与我们的类似物复合的大肠杆菌甲基丙二酰辅酶 A 脱羧酶的结构提供了对底物结合和催化机制的深入了解。与直觉相反，我们类似物的带负电荷的磺酸盐和硝基官能团结合在活性位点疏水口袋中。脱羧后，烯醇中间体被组氨酸质子化，防止 CO2-烯醇重组，产生丙酰辅酶 A。活性测定支持组氨酸催化酸并揭示该酶显示出显着的水解活性。我们的结构还提供了对这种水解活性的洞察。我们的类似物以低微摩尔 Ki 值抑制脱羧/水解活性。该研究开创了使用具有羧酸等排体的丙二酰辅酶A类似物来研究酰基辅酶A羧
• COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATION AND LIPID DISORDERS
  申请人：Kandula Mahesh

  公开号：US20150057347A1

  公开（公告）日：2015-02-26

  The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing inflammation and lipid disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of hypertriglyceridemia, steatohepatitis, cystinosis and inflammatory diseases.

  该发明涉及公式I和公式II的化合物或其药用可接受的盐，以及其多晶型、溶剂合物、对映体、立体异构体和水合物。包括有效量的公式I或公式II化合物的药物组合物；以及用于治疗或预防炎症和脂质紊乱的方法可以制成口服、颊内、直肠、局部、经皮、经粘膜、静脉、肠道给药、糖浆或注射剂。这种组合物可用于治疗高三酸甘油酯血症、脂肪肝、半胱氨酸症和炎症性疾病。
• One-pot chemo-enzymatic synthesis of reporter-modified proteins
  作者：Andrew S. Worthington、Michael D. Burkart

  DOI：10.1039/b512735a

  日期：——

  To meet recent advancements in the covalent reporter labeling of proteins, we propose a flexible synthesis for reporter analogs. Here we demonstrate a one-pot chemo-enzymatic synthesis of reporter-labeled proteins that allows the covalent tethering of any amine-terminal fluorescent or affinity label to a carrier protein or fusion construct. This two-reaction sequence consists of activated panthothenate coupling, biosynthetic conversion to the coenzyme A (CoA) analog, and enzymatic carrier protein modification via phosphopantetheinyltransferase (PPTase). We also probe substrate specificity for CoAA, the first enzyme in the pathway. With this approach CoA analogs may be rapidly prepared, thus permitting the regiospecific attachment of reporter moieties from a variety of molecular species.

  为了应对蛋白质共价报告标记领域的最新进展，我们提出了一种灵活的报告模拟物合成方法。在此，我们展示了一种一锅法化学酶合成带有报告标记的蛋白质的技术，该技术能够在载体蛋白质或融合构建体上共价连接任何氨基末端荧光或亲和标记。这一双反应序列包括活化的泛酸结合、生物合成转化为辅酶A（CoA）模拟物，以及通过磷酸泛酰巯基乙胺转移酶（PPTase）进行的载体蛋白质修饰。我们还探究了该途径中第一个酶CoAA的底物特异性。通过这种方法，CoA模拟物可以迅速制备，从而允许各种分子种类的报告基团在特定位置进行连接。